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TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by
1Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Abstract:
It has long been postulated that protein tyrosine phosphatases may act as tumor suppressors because of their ability to counteract the oncogenic actions of protein tyrosine kinases. Here we report the cloning and characterization of a novel human protein tyrosine phosphatase, TEP1. TEP1 contains the protein tyrosine phosphatase signature motif, and we show that it possesses an intrinsic protein tyrosine phosphatase activity. TEP1 also shares extensive homology with tensin, a cytoskeletal protein localized to focal adhesions, and with auxilin, a protein involved in synaptic vesicle transport. Immunofluorescence studies show that TEP1 is a cytoplasmic protein. The abundance of TEP1 transcription is altered in many transformed cells. In the transforming growth factor beta-sensitive cells, TEP1 expression is rapidly down-regulated by transforming growth factor beta, a cytokine shown to be involved in regulating cell adhesion and cell motility. We have also mapped the gene encoding TEP1 to chromosome 10q23, a locus that is frequently deleted in a variety of human cancers. TEP1 protein is identical to the protein encoded by the candidate tumor suppressor gene PTEN/MMAC1. Our functional studies of the TEP1 protein suggest that its tumor suppressor function may associate with its intrinsic protein tyrosine phosphatase activity and its cytoplasmic localization.
Insights
We identified a novel human protein tyrosine phosphatase, TEP1, with tumor suppressor potential. Its expression is altered in cancer cells, and it shares identity with the PTEN/MMAC1 gene.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Protein tyrosine phosphatases (PTPs) are investigated as potential tumor suppressors due to their role in opposing oncogenic protein tyrosine kinases.
- The function and regulation of PTPs in cellular transformation and cancer development are not fully elucidated.
Purpose of the Study:
- To clone and characterize a novel human protein tyrosine phosphatase, TEP1.
- To investigate the potential tumor suppressor role of TEP1 and its relationship with known cancer-associated genes.
Main Methods:
- Cloning and characterization of the TEP1 gene.
- Assays to determine protein tyrosine phosphatase activity.
- Homology searches with known proteins (tensin, auxilin).
- Immunofluorescence microscopy for protein localization.
- Analysis of TEP1 transcription levels in transformed cells.
- Gene mapping to chromosome 10q23.
- Comparison with the PTEN/MMAC1 gene.
Main Results:
- TEP1 possesses intrinsic protein tyrosine phosphatase activity and the characteristic PTP motif.
- TEP1 shares homology with cytoskeletal protein tensin and synaptic vesicle protein auxilin.
- TEP1 is localized in the cytoplasm.
- TEP1 transcription is altered in transformed cells and down-regulated by transforming growth factor beta.
- The TEP1 gene is located at chromosome 10q23, a region frequently deleted in cancers.
- TEP1 protein is identical to the protein encoded by the PTEN/MMAC1 gene.
Conclusions:
- TEP1 is a novel human protein tyrosine phosphatase with significant homology to tensin and auxilin.
- TEP1 exhibits tumor suppressor characteristics, potentially linked to its phosphatase activity and cytoplasmic localization.
- The identification of TEP1 as PTEN/MMAC1 provides further insight into its role in cancer biology and the 10q23 tumor suppressor locus.